The objectives of the proposed studies can be summarized as follows: (A) To continue to define subcategories of "broad spectrum" immunologic deficiency syndromes, based on inheritance patterns, results of immunogenetic and biochemical assays, and differences in response to immunotherapy, and to search for correlations, if any, with clinical differences. The WHO Expert Committee on Immunodeficiency has stated that their current classification of immunodeficiency disorders is admittedly incomplete, and indeed several disease entities listed as such have since been shown to be heterogeneous syndromes. (B) To search for close associations and possible linkage between one or another subcategory of immunodeficiency syndrome and immunogenetic markers, and to continue investigations aimed at the definition of "new" allotypic markers of human immunoglobulins. (C) To continue the development of new test methods for further assessment of deficiencies in those cells associated with immunodeficiency (e.g., T and B cell populations and subpopulations, monocytes, granulocytes). (D) To investigate possible immunogenetic predisposition to several diseases of "unknown etiology" (e.g., mu ltiple sclerosis, alopecia totalis) which are associated with inadequate or inappropriate immunologic response of one or another immunocyte population in hosts possessing rare "deficient" immune response genes to the (unknown) etiologic agent involved (microbial, viral, etc.), and to continue our studies of cystic fibrosis, which is characterized by abnormal immunocytes and abnormal immunocyte products. We propose that many such diseases can best be understood as immune deficiency diseases of "diseases of immunologic aberration" and that more effective modes of therapy can be devised on this basis. (E) To study the number and function of immunocyte populations in "antigen selective" immune defects (severe recurrent infection with a single organism), and to determine whether such patients have an immunogenetic predisposition due to rare immune response genes. (F) To search for human antigens defined by immune response genes, using alloantisera produced previously by prolonged cross immunization, to test the hypothesis that rare "broad spectrum" and "antigen selective" immune deficiencies are associated with unusual immune response genes.